Cartilage repair, preservation and growth by stimulation of bone-chondral interface and delivery system and methods therefor

ABSTRACT

Therapeutics and methods of treatment to repair, preserve and grow cartilage are presented. In addition, systems and methods for delivering a therapeutic to a hard to reach anatomical area, such as, for example, the BCI, are presented. A cannulated delivery device provided with a cutting tip, cutting flutes and threads on its distal end can be provided. Using such an exemplary device, various novel therapies for joint and cartilage repair, preservation and generation can be implemented. The device may have two-needles, with a first cannula/needle, with a finger grip at its distal end, and a longer inner needle to penetrate through the outer needle into the disc, and introduce therapeutics, for example, via a syringe. When provided with a septum at the inner needle&#39;s proximal end, the PIARES device is a completely closed system, and its use minimizes trauma.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of U.S. patent applicationSer. No. 17/681,768, filed Feb. 26, 2022, now U.S. Pat. No. 11,759,236,which is a continuation of U.S. patent application Ser. No. 16/862,448,filed Apr. 29, 2020, now U.S. Pat. No. 11,389,196, which is acontinuation of U.S. patent application Ser. No. 15/819,751, filed Nov.21, 2017, which is a continuation of U.S. patent application Ser. No.13/861,360, filed Apr. 11, 2013, now U.S. Pat. No. 9,827,010, whichclaims priority to U.S. Provisional Patent Applications No. 61/686,835,filed on Apr. 11, 2012, and 61/800,574, filed on Mar. 15, 2013, eachentitled “CARTILAGE REPAIR, PRESERVATION AND GROWTH BY STIMULATION OFBONE-CHONDRAL INTERPHASE AND DELIVERY SYSTEM AND METHODS THEREFOR”. Allof these are hereby incorporated herein by reference.

TECHNICAL FIELD

The present invention relates to various novel treatments fordegenerative joints and discs, and improved devices and therapies forthe delivery of therapeutic agents to hard to reach anatomical areaswith minimal trauma so as to better implement such novel treatments.

BACKGROUND OF THE INVENTION

Conventional Therapies for Degenerative Disc and Other Cartilage Disease

Considering knee degeneration or osteoarthritis (“OA”) as an example,pain in knee OA, defined as loss of articular cartilage in the knee, isthought to be caused by increased pressure on the subchondral bone.Thus, there are changes in subchondral bone marrow that can be seen atthe earliest stages of the onset of OA (Lorieg et al, Rheum 7: 43-49,2011). Current technologies for treating knee OA include non-steroidalanti-inflammatory drugs (Nsaids) including the newer Cox-2 inhibitors.Although these medications decrease inflammation and pain, theirprolonged use (i) is thought to have an adverse impact on cartilage and(ii) comes with complications of increased risk of hypertension,coronary artery disease, renal failure (especially in diabetics) andpeptic ulcer disease.

Hyaluronic acid (HA) has been shown to have some positive impact oncartilage. However, it has limited success rates in treating knee OA.Thus, while some studies show good success rates, others show ratherpoor ones. Furthermore, success rates decrease substantially in thosepatients with moderate to severe knee OA.

Microfracture has been used for a very small subset of knee OA patientswith small cartilage defects. This technique has seen limited successrates. The technique functions by creating fibrocartilage. However, ifdone excessively, microfracture can sometimes even accelerate the rateof cartilage loss.

Finally, total and partial knee replacements have been used. Theseprocedures have significant complication rates of blood clots andinfections, are expensive, require hospital stays, have the associatedliability of inserting metal in the body, and come with markedlyincreased healthcare costs.

Conventionally, when delivering a therapeutic agent to a hard to reachanatomical area, such as, for example, the bone-chondral interface(BCI), a drill is used to create a pathway. Generally, a device with acentral cannula is used, which is initially provided with a miniaturedrill shaft and drill bit within it. The practitioner drills into thebone, and then removes the drill shaft and bit from the central cannula.Then a stylet is inserted, thus isolating the bone tissue from theoutside environment. Finally, the stylet is removed and one of variousappropriate therapies (e.g., drug, biologic or therapeutic) can bedelivered via a syringe or other delivery device.

This conventional procedure thus twice exposes the internal tissue toambient air. Once when the drill shaft and bit are removed and replacedwith a stylet, and again when the stylet is removed to introduce atherapeutic agent. Each time internal tissues are exposed in this waythe risk of infection increases. Furthermore, this is technically morechallenging and time consuming with increased risk of complications.

What is thus needed in the art are exemplary devices and methods toreach internal anatomical areas which at the same time decreases theexposure of internal tissues to ambient air and reduces trauma. What arefurther needed in the art are therapeutics and methods of treatment toaddress loss of cartilage, and devices that enable simpler delivery ofsuch therapeutics in less time, with reduced trauma, so as to reduce therisk of complications.

BRIEF DESCRIPTION OF THE DRAWINGS

It is noted that the application file contains at least one drawingexecuted in color. Copies of this patent application with color drawingswill be provided by the U.S. Patent Office upon request and payment ofthe necessary fee.

FIGS. 1A and 1B, are a set of two images entitled “Example APre-operative” and “Example A Post-operative” from an example test caseaccording to an exemplary method of the present invention, describedbelow as “Example A” under the Experimental Results portion of thisdisclosure. These images relate to the case described in the independentradiologist's report provided in Appendix A.

FIGS. 1C and 2 are preoperative scans of an individual's knee;

FIGS. 3-4 are corresponding scans of the individual's knee aftertreatment according to the methods of exemplary embodiments of thepresent invention;

FIG. 5 is a side-by-side comparison of another individual's knee beforeand after treatment according to the methods of exemplary embodiments ofthe present invention;

FIG. 6 is an exemplary distal end of an exemplary bone-chondralinterface (“BCI”) delivery device according to exemplary embodiments ofthe present invention;

FIG. 7 is an exploded view of an exemplary delivery device according toexemplary embodiments of the present invention (top panel), and amagnified view of an exemplary proximal portion of the exemplarydelivery device (bottom panel);

FIG. 8 is a further magnified view of an exemplary proximal portion ofthe exemplary delivery device of FIGS. 6-8 ;

FIG. 9 depicts an alternate exemplary embodiment of the exemplarydelivery device of FIG. 6 ;

FIG. 10 depicts an exemplary delivery device which may be known as a“Percutaneous Intradiscal Annular Repair System” (PIARES”), directed topercutaneous intradiscal annular repair according to exemplaryembodiments of the present invention;

FIG. 11 depicts a variant embodiment of the exemplary delivery device ofFIG. 10 ;

FIG. 12 depicts detailed views of an exemplary delivery device accordingto an embodiment of the present invention directed to bone-cartilageinterfaces of peripheral joints and spine;

FIG. 13 depicts an exemplary delivery device being inserted into thebone above and below a right knee according to exemplary embodiments ofthe present invention;

FIG. 14 depicts a magnified view of the knee joint, and adjacent tibiaand femur from the drawing shown in FIG. 13 ;

FIG. 15 depicts details of the distal portion of the exemplary deliverydevice of FIGS. 13-14 ;

FIG. 16A depicts an overview an overview of an alternate exemplary“PecaBoo” delivery device according to exemplary embodiments;

FIG. 16B depicts a tri-lobe handle of the exemplary delivery device ofFIG. 16A;

FIG. 16C depicts a longitudinal cross section of the exemplary deliverydevice of FIG. 16A;

FIG. 17A depicts a drill portion of the exemplary delivery device ofFIG. 16A;

FIG. 17B depicts an exemplary o-ring of the exemplary delivery device ofFIG. 16A;

FIG. 17C depicts an exemplary impact cap of the exemplary deliverydevice of FIG. 16A;

FIG. 17D depicts a tri-lobe handle of the exemplary delivery device ofFIG. 16A;

FIGS. 18A, 18B and 18C illustrate the exemplary delivery device of FIGS.16A-16C and 17A-17D, in two longitudinal views and a longitudinal crosssection, respectively;

FIGS. 18D, 18E and 18F depict magnified views of FIGS. 18A, 18B and 18C,respectively, with additional detail;

FIG. 19A depicts top and bottom views of the exemplary device of FIGS.18A and 18B;

FIG. 19B depicts solid perspective views of the exemplary device of FIG.19A;

FIG. 19C depicts a magnified view of the tip of the exemplary device ofFIG. 19B;

FIG. 20 illustrates exemplary details of an impact cap;

FIGS. 21A through 21D depict an elongated form of the exemplary PecaBoodevice of FIGS. 16-20 , such as may be used for hip procedures;

FIGS. 22A and 22B illustrate the exemplary PecaBoo device (hip length)as inserted into the superior and inferior compartments adjacent to anexemplary hip joint; and

FIGS. 23-48 depict an exemplary prototype of the PecaBoo tool shown inFIGS. 16-20 as used on a patient in an exemplary procedure on the knee,with corresponding high quality X-Ray images of various stages of theexemplary procedure.

SUMMARY OF THE INVENTION

Novel therapeutics and methods of treatment to repair, preserve and growcartilage are presented. In addition, systems and methods for deliveringa therapeutic to a hard to reach anatomical area, such as, for example,the BCI, are presented. In exemplary embodiments of the presentinvention, a cannulated delivery device provided with a cutting tip andthreads on its distal exterior can be provided which has considerableadvantages over conventional devices. These include, for example, (i)ease of manufacture, (ii) use of the exemplary device being faster thanconventional approaches, with both less table time and less steps, (iii)lesser exposure of internal tissues to ambient air, and thus less riskof infection, and (iv) lesser technical complexity leading to lessercomplications. Using such an exemplary device, various novel therapiesfor joint and cartilage repair, preservation and generation can beimplemented. Various versions of such a device are disclosed.Alternatively, for disc repair, a delivery device directed topercutaneous intradiscal annular repair, or “PIARES” device can be usedto introduce therapeutics intradiscally. The device is a two-needledevice, with a first cannula/needle, with a finger grip at its distalend, and a longer inner needle, which can then penetrate through theouter needle into the disc, and can then, for example, be used tointroduce therapeutics, for example, via a syringe. When provided with aseptum at the inner needle's proximal end, the PIARES device becomes acompletely closed system, and its use minimizes trauma.

Thus, in exemplary embodiments of the present invention, a surgical handtool can be provided, used for the non-invasive placement and deliveryof therapeutics, to a targeted site. This can be done through minimallyinvasive skin incision, or without any incision, as maybe desired. Thedelivery and placement of the therapeutic can be controlled and does notneed a powered drill or guide wire.

An exemplary device can have a closed pointed end, a threaded portion,and be provided with thread cutting/forming features, such as flute(s),and can have a shaft perforations to the central lumen at a distal endto deliver therapeutics or other preparations. At the proximal end,means can be provided to attach a syringe in communication with theshaft's central lumen, and there may be a keyed engagement feature forattachment of a hand grip. The delivery device can be made of sufficientlength to reach bone on either side of a desired or targeted joint, andto easily penetrate soft tissue and cortical bone to reach a targetedsite in cancellous bone adjacent to a cartilage defect.

The device's main shaft or drill portion can be made of hardenedstainless steel, or the like, such as, for example, 400 series or 17-40stainless steel, for example.

The device can have, for example, an attachable/removable hand grip forease of placement of the drill bit to a site, with a solid proximal endwith which to tap or hammer, and with a grip for torquing the devicethrough cortical bone and to guide a threaded shaft to a targeted sitein cancellous bone, for example. The grip can have an ergonomic form forease of use, such as a tri-lobe handle, which mimics the natural turn ofa wrist in 120 degree increments.

The device can have an impact cap to (i) provide impact anvil surface toprotect a proximal luer during impaction, as well as to (ii) close theluer opening to a shaft lumen.

DETAILED DESCRIPTION OF THE INVENTION

While the exact cause of knee OA remains unknown, it is stronglybelieved by the inventors that alterations in the bone-cartilageinterface (“BCI”) are present at the earliest stages of knee OA.Therefore, therapies for treating knee OA must target the BCI. Thisapproach can further be extended to other areas where cartilage has beendamaged or lost.

As described below, methods according to exemplary embodiments of thepresent invention address the BCI where early alterations can accelerateknee OA. In exemplary embodiments of the present invention, methods areprovided to stimulate the subchondral bone marrow and expose themesenchymal stem cells (MSCS) that come out of the bone marrow as aresult, to growth factors from platelet-rich plasma (PRP) and very smallembryonic like cells (VSELs). VSELs are known to be released after aninjury resulting in enhanced repair in the animal stroke model (Kucia etal: Cell Tissue Research 331: 125-134, (2008). This enhances cartilagerepair and possible regeneration. As is known, MSCSs exposed to PRPdifferentiate into chondrocytes (Mishra, et al: Tissue Eng. Methods 15:431-435 (2009)).

Methods according to exemplary embodiments of the present invention havea very low risk of infection, are significantly less expensive thanmajor surgical procedures, and avoid the liability of metal implants orNSAID medications. Furthermore there is very little down time forpatients undergoing this procedure inasmuch as it is performed on anoutpatient basis with a quick return to work.

I. Exemplary “Ground Up” Methodology for Cartilage Repair

In exemplary embodiments of the present invention, cartilage issues canthus be treated from the “ground up.” Such an approach is analogous tohow in agriculture plants are often treated by accessing their roots.Thus, in exemplary embodiments of the present invention, technologiescan be used that target the bone-cartilage interface (BCI) to treatcartilage issues, as opposed to conventional “top down” approaches suchas, for example, the current undesirable practice of microfracture. Asnoted above, microfracture creates fibrocartilage with very limitedsuccess in patients with cartilage defects. Moreover, microfracture canonly be used for a very small subset of knee osteoarthritis (“OA”)patients—only those having small cartilage defects. If it is doneexcessively it itself can even lead to accelerated cartilage loss.

Thus, in exemplary embodiments of the present invention, novelmethodologies for the treatment of degenerative joints and discs can beutilized. This can be applied, for example, to the knee, to treat medialjoint knee degenerative disc disease (“DJD”) using the followingprotocol, for example:

Day 1:

-   -   350 mcg of Granulocyte Colony-Stimulating Factors (“GCSFs”)        injected subcutaneously;

Day 2:

-   -   350 mcg of Granulocyte Colony-Stimulating Factors, or GCSFs        injected subcutaneously (this second GCSF injection is        optional);    -   Draw blood and spin it down to obtain 4 cc of Platelet Rich        Plasma (“PRP”) in total;    -   Put 1 cc of the PRP into the tibial medial compartment by        drilling and injecting at the bone-cartilage interface (“BCI”),        followed by injection of 0.1 cc of 10% calcium chloride solution        or thrombin to form a clot.    -   Wait two minutes before reverse drilling out the delivery device        so that a clot may form and keep the PRP from leaking out.        Alternatively, bone wax can be injected to keep the PRP in        place;    -   Put 1 cc of PRP into femoral medial or lateral compartment by        drilling and injecting at the bone-cartilage interface, followed        by injection of 0.1 cc of 10% calcium chloride solution or        thrombin to form a clot.    -   Wait two minutes before reverse drilling out the delivery device        so that a clot may form and keep the PRP from leaking out;    -   Put remaining 2 cc PRP into the knee joint;    -   MRI is done pre-treatment and at 3 months post-treatment.

It is understood that these are exemplary values only. Variations of thequantities of therapeutics can also be used, such as, for example, arange of 1-3 cc of PRP injected each above and below the relevant joint,a range of 0.1-0.3 cc of calcium chloride used afterwards, and a rangeof 2-6 cc of PRP injected into the joint. Additionally, one can waitbetween 2-4 minutes following delivery of the PRP and clotting agent,for example.

It is noted that GCSFs have not heretofore been used for cartilagerepair. An exemplary GCSF that may be used can be, for example,Neupogen.

In exemplary embodiments of the present invention, the PRP can bedelivered via one syringe, and either CaCl, thrombin or bone wax, forexample, can be delivered via another syringe. Alternatively, a skilled,dexterous and quick practitioner may, for example, load both the PRP andCaCl into one syringe, if she can deliver the dose quickly enough sothat no clotting occurs. In exemplary embodiments of the presentinvention this method can be used, and the inventors have successfullydone it in experimental cases.

In exemplary embodiments of the present invention the procedure can, andpreferably should, be performed under fluoroscopy or ultrasound guidanceto insure proper positioning of the delivery devices at the BCI and tofurther insure that there is no penetration through the cartilage, whichwould cause damage.

Following injection of the therapeutic, the delivery device should beleft in place for approximately 2 minutes to make sure a clot is formed.Alternatively, bone wax or the equivalent can be used, for example, toseal the entry instead of calcium chloride.

Exemplary Sterile Kit

In exemplary embodiments of the present invention, an exemplary kit cancontain, for example, two disposable delivery devices, to be used toinject at the BCI in the superior and inferior locations to a joint, asshown, for example, in FIGS. 23-48 . Making them disposable minimizesthe risk of infection. Such an exemplary kit can also be provided with avial of bone wax and a 2 cc vial of 10% calcium chloride solution, forexample. Calcium chloride activates platelets and also forms a clot. Ingeneral, the CaCl can be provided in a 1/10th ratio to the biologic,thus for 1 cc of stem cells and PRP, a 0.1 cc volume of CaCl may beused. Alternatively, in exemplary embodiments of the present invention,the delivery device maybe reusable, and sterilizable, such as a versionof the exemplary PecaBoo device described below. Still alternatively, adevice can have a disposable hub and drill portion (including impactcap—see FIG. 17 ), and a reusable handle, for example.

Rationale—Expose Mesenchymal Cells to PRP to Generate New Cartilage

The rationale behind the inventive protocol is that bone marrow may bestimulated by the GCSFs to produce mesenchymal cells (MSC). As these MSCcells come out of the bone marrow and make their way towards the BCI,they are exposed to the PRP (or, for example, PRP and VSELs) beforereaching the bone-cartilage interface. There is good evidence thatexposure to PRP (or PRP and VSELs) induces the MSCs to become cartilage,or more granularly, the MSCs and VSELs (Very Small Embryonic Like stemcells), when exposed to PRP or hyaluronic acid develop intochondrocytes, which in turn create the cartilage matrix. This isbelieved to be the key factor that has led to the success seen in theknee treated and described in Appendix A, where an approximate doublingof cartilage size (relative to the pre-treatment MRI result) was seen ina post-operative MRI three months following treatment, with markedlyreduced pain. Furthermore, VSELs are released into the peripheral bloodfollowing stimulation with GCSF which, as noted above, helps withcartilage repair. Thus, both PRP and VSELs ma, for example, be deliveredto the femoral and tibial compartments, for example, in an exemplaryknee procedure. Sometimes just drilling is sufficient to stimulatecartilage growth, or to resolve an ischemia. Thus, in various exemplaryembodiments of the present invention, the following various approachescan be used in treating affected joints; in all cases a drill deliverydevice according to the present invention may be used:

-   -   1. Drill alone;    -   2. Drill+PRP+bone wax;    -   3. Drill+PRP+bone wax;    -   4. 300 mcg GCSF in 1-3 injections, then followed by drill, then        followed by VSEL+PRP+{bone wax or CaCl};    -   5. Bone marrow aspirate+CaCl or bone wax;    -   6. Culture expanded autologous stem cells, from stem cell bank;    -   7. Autologous embryonic stem cells, from cord blood;    -   8. embryonic stem cells, from a cell bank; and    -   9. Autologous preserved cells.

Thus, in exemplary embodiments of the present invention, there can be asignificant reduction in the number of knee replacements being done witha concomitantly large reduction in health care costs, inasmuch as theinventive technology does not involve hospitalization or expensiveartificial joints. In exemplary embodiments of the present invention, ifpartial results are seen with one treatment, there is the option torepeat the treatment from three months to two years later for additionaltherapeutic benefit. It is noted that the treatment can be, for example,repeated indefinitely as long as there is therapeutic benefit. Thus,from some patients the treatment can be repeated over decades ifhelpful.

It is noted that in exemplary embodiments of the present invention thebone marrow can be, for example, chemically stimulated with GCSF, whilethe bone marrow can also be stimulated mechanically by creatingmicrotrauma above the bone marrow (“above” in the sense of a directiontowards the knee joint). Such a microtrauma stimulates the bone marrowto produce more MSCS and VSEL cells, and also increases the blood supplyto the bone-cartilage interface to allow for better repair.

EXPERIMENTAL RESULTS Example A

In an experimental trial of treatment methods according to an exemplaryembodiment of the present invention, a 50 year old female with advanceddegenerative osteoarthritic disease of the knee was treated. Prior tothe treatment, a pre-operative MRI was done. Post treatment a threemonth follow-up MRI was performed on the patient and read by anindependent radiologist. Provided hereto as Appendix A is theindependent radiologist's report. As noted in the report, the postoperative MRI showed an increase in cartilage matrix from 1.8 mmpre-treatment to 3.7 mm at the follow-up MRI. Thus, the inventivetechnique shows early promise for cartilage repair and possibleregeneration.

Example B

Imaging data from another experimental case are provided in FIGS. 1-4 .As can be seen therein, FIGS. 1 and 2 are respectively axial andsagittal images of a patient's knee from a preoperative scan. FIG. 1depicts an area of decreased blood flow due to an ischemia, as shown bythe red arrow, also seen in FIG. 2 pointed to by the red and greenarrows. Injections similarly performed according to the above describedprotocol, to the femoral and tibial compartments by drilling andinjecting at the bone-cartilage interface, followed by injections intothe knee joint. FIGS. 3 and 4 are corresponding axial and sagittalimages form a MRI taken three months following the treatment. As can beseen, significant new cartilage has grown, and the ischemia has beenessentially resolved, as shown in FIG. 3 .

Example C

FIG. 5 depicts side by side comparisons of sagittal images of a knee ofa third patient. The left panel is an image form a preoperative scan,and the right panel a corresponding image from a post operative MRI. Asshown in FIG. 5 , the post operative MRI showed an increase in cartilagematrix from 1.60 mm to 1.87 mm at the follow-up MRI.

In exemplary embodiments of the present invention, the therapeuticprotocol described above can similarly be used for osteoarthritis andavascular necrosis, as well as for treating meniscal and labral injuriesin the joints.

Exemplary Variations of the Protocol

In exemplary embodiments of the present invention, variations on theabove-described protocols can be used for other anatomical areas.Examples of these are next described.

Joints—for joints, the step of injecting GCSF for stimulating bonemarrow may be skipped. The drilling/twisting alone of the deliverydevice (as described below) will stimulate bone marrow combined with PRPinjection or injection of other biologics such as, for example, stemcells as an alternative.

Joint Arthritis—there is an alternative method for treating jointarthritis by using adipose tissue derived stem cells that can beinjected intravenously combined with intra-articularly without drillinginto the bone-cartilage interface. If that does not work then analternative method is adipose derived stem cells injected intravenously,intra-articularly and into the bone-cartilage interface. Thiscombination of systemic and local therapy is believed to be the next bigstep in biologic interventions for joint issues.

Spine—in similar fashion as was described above for the knee, for thespine one can inject GCSF on days 1 and 2, followed by extracting PRP onday 2. The PRP can then be drilled into vertebral bodies above and belowthe affected disc along with intradiscal injection and epiduralinjection of the PRP.

Alternatively, one can skip the GCSF and just drill into vertebralbodies followed by injection of PRP into the vertebral body followed bythrombin or calcium chloride to form a clot (so that the PRP does notleak out), and then injecting the PRP, followed by thrombin or calciumchloride, intradiscally. It is noted that for injecting the vertebralbody the novel BCI device described below (FIGS. 6-8 and 12 ) can beused. For an intradiscal injection, standard existing spinal needles canbe used, or for example, a variation of the novel PIARES delivery deviceas shown in FIGS. 10 and 11 .

Finally, another alternative method for treating disc or stenosis issuesof the spine can be, for example, to use adipose tissue derived stemcells which first can be given intravenously along with caudal epiduralinjection. If this does not give results, then the adipose stem cellscan, for example, be given intravenously along with intradiscalinjection and caudal epidural, using, for example, a standard spinalneedle, or, for example, a variation of the novel PIARES delivery deviceas shown in FIGS. 10 and 11 .

II. Exemplary Delivery Devices

In exemplary embodiments of the present invention, the therapeuticmethods described above can be delivered in a safe and efficient mannerusing various novel delivery devices according to various exemplaryembodiments of the present invention, as next described.

Exemplary Delivery Device

FIGS. 6-9 depict an exemplary delivery device according to exemplaryembodiments of the present invention. FIG. 6 depicts an exemplary distalend of an exemplary delivery device according to exemplary embodimentsof the present invention. As can be seen therein, the device isessentially a hollow cannula with threads on the outside of it. Thethreads allow for controlled insertion and removal of the device. It hasa cutting point at its distal end, and immediately proximal to thecutting tip (i.e., above it) a series of holes are provided to dispensevarious therapeutics. As shown in FIG. 6 , the solid slug at the tip ofthe device can be laser welded in place, for example, and the variousholes in the cannula laser cut, for example. Exemplary dimensions areshown in FIG. 6 , but are understood to be merely exemplary, and notlimiting.

Given the solid cutting tip, a user first presets the device with hammertaps, and then can screw in the device a desired length. This can bedone manually, or via a drill interface provided at the distal end ofthe device, for example. As described below, one can, for example, tapwith a hammer to set the device into place into dense cortical bone, andthen subsequently twist (or drill) to advance the delivery device intospongy bone (interior cancellous bone).

FIG. 7 is an exploded view of an exemplary embodiment of the deliverydevice according to the present invention (top panel), and a magnifiedview of an exemplary proximal portion of the exemplary delivery device(bottom panel). With reference thereto, the top panel of FIG. 7 showshow the device has a cannula/needle portion, a needle hub, and a capwith twist grip and a surface at its end for tapping with a hammer. Thecap and needle hub can be connected via keys, which thus insure that thecap and needle hub do not move relative to one another as a user drills,for example, or manually screws/twists in, for example, the device.

Provided at the top of the needle hub can be a needle pierce septum,which allows a sterile syringe to be introduced into the cannula toinject therapeutics or PRP rich blood, as described above, afterremoving the cap, once the device is in the proper position. Thus, usingsuch a septum, the tissue exposed to the distal end of the deliverydevice need never contact open air, and the delivery system is thustotally closed. The septum can be made of silicone, for example, orother appropriate materials.

FIG. 8 is a further magnified view of the distal portion of theexemplary device of FIG. 7 . FIG. 9 depicts an alternate exemplaryembodiment of an exemplary delivery device of FIG. 7 , where the cap isscrewed on to a luer provided at the distal end of the cannula/needle.

Exemplary Delivery Device for Discs—PIARES

FIGS. 10-12 depict an exemplary delivery device directed to percutaneousintradiscal annular repair according to exemplary embodiments of thepresent invention. This device is known as a “PIARES” device by theinventors, and is used for introducing therapeutics intradiscally, asdescribed above. Such a device is inserted by hand, in most cases. Thedevice is a two-needle device, and can have, for example, a firstcannula/needle, with a finger grip and luer hub at its distal end. Thecannula can be, for example, 16 gauge, and be approximately 3.5 incheslong, for example, but such dimensions are exemplary and not limiting.There can be provided a stylette, to fit within the cannula, of, forexample, 21 gauge (for a 16 gauge cannula). The stylette can lock ontothe distal end of the luer, at a luer lock hub. The stylette can remainin the outer needle as a user inserts the device near a disc (but notall the way to the disc), then be removed so as to allow the insertionof the longer inner needle, which can then penetrate into the disc, andcan then, for example, be used to introduce therapeutics, for example,via a syringe.

FIG. 10 thus also shows, at the bottom of the figure, the second, orinner needle of the device. This inner needle fits inside the firstneedle/cannula, and protrudes from it into the disc. The inner needlecan be, for example, 5 inches in length, where the bottom 20 mm or sohave perforations out of which the therapeutic agents can diffuse intothe patient. Such a device can have, for example, a cannula of 21-25gauge. It can have a similar luer and finger grip, and can similarlyaccept a syringe which can lock on its luer lock hub, to deliver thetherapeutics, as described above. There is no stylette for this innerneedle, obviously.

FIG. 11 depicts a variant embodiment of the exemplary PIARES deliverydevice of FIG. 10 , where instead of a luer lock hub at the proximal endof the inner needle, a septum is provided, thus completely isolating thedelivery device and the disc into which the inner needle protrudes fromexposure to the ambient space. To introduce therapeutic agents into theinner needle and thus out the distal holes into the disc, a user insertsa needle into the septum, in similar fashion as shown in FIG. 12 for theperipheral joint and spine embodiment of the delivery device.

Thus, in operation, a user first inserts the outer needle, with styletteinside. This is done under imaging guidance, such as, for example,fluoroscopy or ultrasound. The outer needle is placed near, but not allthe way towards, the relevant disc. The stylette is then removed, andthe inner needle inserted inside the outer needle. Thus, as shown, theouter needle can be 16 gauge, and the inner needle from 21 to 25 gauge,for example. Because it is longer than the outer needle, for example, 5inches versus 3.5 inches, as shown in FIGS. 10-11 , the inner needleprotrudes out the end of the outer needle, and can be guided into thedisc itself. Now at this point the distal end of the inner needletouches the disc, but if the septum embodiment of FIG. 11 is used on theinner needle, the system is completely closed. Once intradiscal,therapeutic can be introduced via the inner needle.

Thus, the PIARES device has a number of novel advantages: (i) itprovides a fully and completely closed system when the septum is used onthe inner needle's proximal end; (ii) therapeutic can be deliveredsimultaneously to the nucleus and annulus of the disc, thus to delivertherapeutic to where the tear is; and (iii) by using the outer needlefor initial positioning, and then granularly positioning the longerinner needle, which is then fully set up to deliver therapeutic agents,trauma to the disc is minimized, as opposed to conventional approacheswhere needles are moved in and out. Less trauma means quicker healingand better disc repair.

FIG. 12 depicts detailed views of an exemplary delivery device accordingto an embodiment of the present invention directed to deliveringtherapeutics to bone-cartilage interfaces of peripheral joints andspine. It is a more detailed drawing of the exemplary device shown inexploded view at the top panel of FIG. 7 , with a perspective view. Asseen in FIG. 12 , there can be a cutting tip, and proximally from itexternal screw threads between which are interspersed perforations. Thusthe grip is first tapped with a hammer for initially setting it intoplace into dense cortical bone, and then subsequently twisted by a userto advance the delivery device into spongy bone (interior cancellousbone). The cannula can be from 14 to 16 gauge, for example, and at theproximal tip of the device there can be a needle pierceable septum seal,for example, or a luer lock with removable cap such that a syringe canbe attached, as shown in various other embodiments and as describedabove.

While the shown version has a flat distal surface for tapping a hammerfor the initial setting, in other exemplary embodiments an interface canbe provided in the center of the end of the cap, to interface withcommonly used drills, for example.

Illustrations of Delivery Device as Used in Knee Procedures

FIGS. 13-15 illustrate exemplary use of the device of FIGS. 6-9 in kneeprocedures. FIG. 13 depicts an exemplary delivery device being insertedinto the bone above and below an exemplary right knee according toexemplary embodiments of the present invention. Because this is aperipheral joint, the device of FIG. 12 would be used. As can be seen inFIG. 13 , the device is generally inserted above and below the affectedjoint, and is inserted so as to be close to the interior edge of thecortical bone, above and below the cartilage of the affected joint. Inthe case of the knee joint depicted, one delivery device is insertedabove and below the articular cartilage of the knee. As described above,using the protocol described above, the therapeutic introduced by thepractitioner or user diffuses from the holes in the distal end of thecannula, and the bone marrow is stimulated by a GCSF to producemesenchymal cells (MSC). As these cells come out of the bone marrow andmake their way towards the BCI they get exposed to PRP before reachingthe bone-cartilage interface. The exposure to PRP is believed to thusinduce the MSCs to become cartilage.

FIG. 14 depicts a magnified view of the knee joint, and adjacent tibiaand femur as shown in FIG. 13 , further illustrating the diffusion oftherapeutic(s) uniformly away from the cannula. FIG. 15 depicts detailsof the distal portion of the exemplary delivery device of FIGS. 13-14 ,showing the threads and the holes interspersed between them, at variousrotational orientations of the delivery device.

Alternate Exemplary Delivery Device—“PecaBoo”

FIGS. 16A-21 are detailed design drawings of an alternate improvedexemplary delivery device tool according to an exemplary embodiment ofthe present invention. Variations of this device ma, for example, beused in knee, hip and other joint procedures. This alternate deliverydevice is next described.

An exemplary prototype of the tool of FIGS. 16A-20 was fabricated, andtested on various patients with DJD of the knee with excellent results.The exemplary tool may be known and/or marketed under the trade name“PecaBoo.”

FIGS. 16A-21D, next described, illustrate two versions of an exemplarydelivery device according to exemplary embodiments of the presentinvention. With reference to FIG. 16A, this is an overall view of thedevice. The device has three primary parts: a drill portion, an impactcap and an ergonomic tri-lobe handle. The tri-lobe handle is shown withits top and bottom views, respectively, in FIG. 16B. As can be seen onthe top of the tri-lobe handle there is a built in metal pad shown, forexample, in FIG. 16C, at the far right image, which occupies almost allof the space of the top portion of the tri-lobe handle. This metalportion can be used once taken off the tool and turned around as a kindof a hammer, mallet or tapping device to push in the drill, when coveredby the impact cap, into a patient's bone. The impact cap prevents damageto the hub in such a use. It is noted that the exemplary dimensionsprovided in FIGS. 16A-21D are exactly that, exemplary, and this is oneof many prototypes that can be built according to various exemplaryembodiments of the present invention. The dimensions are left forillustrative purposes only to provide exemplary aspect ratios, as wellas exemplary dimensions, for a tool that has been found to be convenientto certain practitioners.

With reference to FIG. 16C, which is a longitudinal cross section of theexemplary tool, there is a tight slip fit between the tri-lobe handleand the drill portion of the tool, such that the handle tightly fitsupon the tool such that it can be turned and manipulated. Also seen inthe cross section is the impact cap which covers the luer at theproximal end of the drill as illustrated in more detail in the followingfigures. It is noted that in these figures the drill is referred to as“drill 16.” The “16” refers to an internal design identifier.

With reference to FIGS. 17A-17D, there is seen the drill with integralhub at 17A, an O-ring which slips over the hub at 17B, the impact capreferred to above, at 17C and the tri-lobe handle at 17D. These fittogether as shown, where the O-ring is slipped over the top of the drillwith integral hub so that it sits as shown in FIG. 16C. This thencreates the tight slip fit of the tri-lobe handle on the hub.Alternatively, C clip rings can be used instead of an O-ring—which wouldneed to be replaced after some time—or, for example, other attachmentmechanisms as may exist in the art. The impact cap shown in FIG. 17Ccovers a female luer lock such that the drill is totally closed and notexposed to the air any more than absolutely necessary. The impact capallows the tri-lobe handle, as shown at 17D, to be removed from theremainder of the tool and still allow the tool to be a completely closedsystem. Moreover, a practitioner can, upon removing the tri-lobe handleas noted above, turn it around such that the metal place built into thetop of it can be used to tab on the impact cab shown as FIG. 17C withoutdamaging or affecting the rest of the tool, namely the drill withintegral hub shown at FIG. 17A. In exemplary embodiments of the presentinvention the drill may be disposable and the handle reusable, or theentire device autoclavable and reusable.

FIGS. 18A-18F illustrate the exemplary delivery tool of FIGS. 16 and 17in various longitudinal views and longitudinal cross section. Withreference to FIG. 18A the female locking luer is shown at the far rightas well as the integral hub upon which, for example, an O-ring (as shownat FIG. 17B) can be placed to provide a tight slip fit. Additionally,FIG. 18A shows, for example, a 2.0 pitch helix to the cutting threadsand illustrates further that the tip of the drill can be coated with acoating such as, for example, titanium nitride, or TiN. TiN is anextremely hard ceramic material which is often used as a coating ontitanium allows, steel, carbide and aluminum components to improve thesubstrate surface properties. Because of these hardening properties,such a coating can be used to protect cutting and sliding surfaces ofmedical devices, and it is also used as a non-toxic exterior for medicalimplants, making it ideal to improve the hardness and cutting ability ofthe tip of the exemplary delivery tool and at the same time be medicallyinured to the patient's tissues. As before, exemplary dimensions areprovided in FIG. 18 , and they are, of course, simply illustrative andnot intended to bind or limit the invention in any way. FIG. 18Billustrates the O-ring gland, and an exemplary laser weld if the drilland hub are decided to be made in two pieces. Alternatively, they can bemade in one piece and machined. FIG. 18B also illustrates how the drillcan be made of 455 stainless steel cannulated bar stock, for example.Other metals and stainless steel grades are also usable, in variousexemplary embodiments.

FIG. 18C, the longitudinal cross section, again shows exemplarydiameters, which are only illustrative. This figure also illustratesthat the drill with integrated hub can be fabricated as one piece andthat the tip of the drill has a straight portion, as well as a taperedportion occupying the most distal portion of the delivery device, tomake it more easily insertable into a patient. There are also seen inthe depictions of FIG. 18 at the tip of the device some grooves slightlydistal to the actual tip which are shown in greater detail in FIGS. 19Athrough 19C. Finally, the tip can be laser welded to the cannulateddrill portion, as shown in FIG. 18C.

FIGS. 18D through 18F are copies of FIGS. 18A through 18C, respectively,somewhat magnified, with further explanatory notes by the presentinventors. With reference to FIG. 18D one can see that there areperforations in the distal tip of the exemplary delivery device, ascalled out by the inventor notes. These perforations are the holes bywhich the fluid is delivered. In a variation from that shown in thedevice of FIGS. 13 and 14 , in this exemplary embodiment there are onlya few holes. Actually two full perforations across the entire diameterof the distal tip of the exemplary device, making four holes in total,located only at the most distal portion. Of course, they have to beproximal to the point at which the spade-type cutting tip, as shown inFIGS. 18E and 18F, but they can be immediately proximal of that as shownin FIG. 18F. It is found that a smaller number of holes placed at theextreme distal portion of the exemplary tool or delivery device allowthe therapeutics to be delivered closest to the bone chondral interface.Thus, once a practitioner has screwed in the device as far as he needsit to be (and this is done under fluoroscopy as described above, and asshown in the photographs of actual procedures described below) he or shecan then unscrew the device slightly, moving it back, and dispense themedication into the cavity created at the tip of the device by slightlymoving back the device or unscrewing the device. The physician can, forexample, unscrew slightly and deliver medication, and repeat thisprocess a few times, and thereby fill up a section of the channelcreated. This ensures that the medication goes to where it is mostuseful, and does not leak out the back of the device.

Also shown in FIG. 18D there are thread cutting flutes which are shownin a magnified depiction immediately beneath FIG. 18D. These are, asdescribed above, used to cut the bone as the drill is turned by a useras it is protruding into the patient's bone. Additionally, one can seethe taper of the distal tip as shown in the drawing below FIG. 18D, andthe fact that the tip itself can be laser welded all around to make surethat it is well fastened within the cannula. FIG. 18E also depicts anexemplary internal thread diameter—or minor diameter—of the threadedportion of the tool, as well as the external thread diameter—also knownas the major diameter. The tapered thread portion of the distal portionof the tip is illustrated in FIG. 18E.

Finally, FIGS. 18D and 18E illustrate the engagement key by which thehub may be attached to the handle, and further depict the threaded luerlock engagement by which that occurs. Moreover, in FIG. 18F the variousportions proceeding from the proximal to the distal end of the exemplarydrill are shown, from right to left, beginning with the female luer, thehub, the cannulated shaft, the center lumen, the threads, and the“spade” type cutting tip. The attachment of the hub to the cannulatedshaft, if it is two pieces, can be by welding all around or in twoplaces, or, for example, the combination of hub and drill, i.e. thecannulated shaft, can be fabricated as one piece and formed bymachining.

FIGS. 19A through 19C illustrate an overall exemplary dimensionalrelationship between the drill with integrated hub and the threadeddistal portion thereof. For example, the threads can occupyapproximately 30% of the overall length of the drill with integrated hubin one example. Again, as noted above, these dimensions are purelyillustrative and various other dimensions and dimensional relationshipscan be implemented in various exemplary embodiments of the presentinvention, all within the scope of the present invention.

FIG. 19A illustrates the drill with integrated hub without the impactcab and without the handle. Within FIG. 19A, a section of the tip islabeled as “D” and that is presented in FIG. 19B in a greatly magnifiedview. This tip contains both the fluid side ports by means of whichtherapeutics and/or liquids are dispensed into a patient using theexemplary delivery device, as well as various cutting features. There isa spade drill point which has essentially a flat surface on two sidesand cutting edges at the tip. This makes for much easier cutting than afully cylindrical shape. Once the spade point is inserted, when the userturns it creates a cylindrical bore. As can be understood, the exemplarydelivery device of FIGS. 16A-19C is, as noted, capable of being slightlypounded or tapped into the bone of a patient above and below, forexample, the knee joint or above and below, for example, a hip joint. Asopposed a simply non-tapered cylinder, it is much easier to penetratethe bone and then cut the bone as the device is turned. This easilycreates a pathway for the drill to proceed through the bone to a pointclose the bone chondral interface. Therefore the combination of (i) thespade drill point, (ii) the thread cutting flutes, and (iii) thetapering of the drill tip, all in combination allow for easy cutting ofthe bone surrounding the tip as a practitioner turns the drill such as,for example, by holding the tri-lobe handle shown in FIG. 17D, or, ifshe has sufficient strength, by simply twisting the integral hub or theimpact cap. In alternate exemplary embodiments some or all of thesefeatures can be provided, but it need not always be necessary to haveall of them.

Along those lines, FIG. 20 illustrates exemplary details of the impactcap. As can be seen, it can be made of 455 stainless steel bar stock, itcan have a straight plunge cut so as to be able to be fastened on thefemale locking luer as shown in FIG. 18 as well as in FIG. 17A, and itcan have exemplary dimensions as shown, for example, or various otherdimensions—the ones shown being completely exemplary and illustrative.

It is noted that the exemplary delivery tool of FIGS. 16A-20 has beenfound useful in treatment of weakened knee joints. As can further bewell understood, for treating the hip joint, the same therapiesdescribed above can be used; however, to deliver the medicines, namelythe PRP, the bone wax or calcium chloride and stem cells, if used, aslightly longer drill would need to be created to penetrate through thefat and muscle to get to the hip joint. Therefore, FIGS. 21A through 21Dillustrate an elongated version of the exemplary drill with integral hubas shown in FIG. 18C for example. As can be seen with reference to FIG.19A (top image), the overall length of the exemplary knee drill deliverytool is 104 mm, but in the case of the exemplary hip embodiment shown inFIG. 21D, the overall length is 205 mm, for example. Other relativedimensions are well within the scope of the present invention, it beinggenerally understood that for most patients it takes a somewhat longerdevice to reach the hip than it does to reach the knee joint.

Other exemplary dimensions of the hip-type drill, are shown in FIGS.21A, 21B, 21C and 21D. The device is essentially the same or similar tothe exemplary knee version of FIG. 18 , except for the length of thedrill itself, and in particular the length of the portion proceeding thetapers that is not threaded. The threaded portion, as shown in FIG. 21D,can be, for example, the same as “Drill 16” which is the project namefor the exemplary knee delivery tool shown in FIGS. 16A-20 . (“Drill 17”being the project name for the exemplary drill for hip joints).

FIGS. 22A and 22B are drawings of the exemplary hip delivery device,namely the “Drill 17” device super imposed on a coronal section of ahuman left hip joint and showing surrounding muscles and tissues. Thenumbers referred to in FIGS. 22A and 22B are provided in the followingTable for background and ease of locating where the exemplary drill isto be placed in exemplary embodiments of the present invention. As canbe seen in the drawing, although this would not be done in practice, forease of illustration, there is one drill shown in the proper positionfor the superior portion of the joint and one for the inferior portionof the joint, although obviously in practice these would generally bedone sequentially and not at the same time.

TABLE OF ANATOMICAL AREAS FOR FIG. 22 1. External iliac artery 2. Psoasmajor 3. Iliacus 4. Iliac crest 5. Gluteus medius 6. Gluteus minimus 7.Greater trochanter 8. Vastus lateralis 9. Shaft of femur 10. Vastusmedialis 11. Profunda femoris vessels 12. Adductor longus 13. Pectineus14. Medial circumflex femoral vessels 15. Capsule of hip joint 16. Neckof femur 17. Zona orbicularis of capsule 18. Head of femur 19.Acetabular labrum 20. Rim of acetabulum 21. Hyaline cartilage of head22. Hyaline cartilage of acetabulum

Exemplary Clinical Use of PecaBoo Device

Next described are FIGS. 23-48 , which are photographs of exemplaryactual procedures on human knees performed using the exemplary PecaBoodevice described above. Procedures were done under fluoroscopicguidance, as noted above, and therefore both photographs of thepatient's knees as well as some of the images from the fluoroscopy willbe provided.

With reference thereto, FIG. 23 shows a practitioner initially insertingthe PecaBoo device into a patient's knee close to the BCI, as describedabove. Similarly, FIG. 24 shows the same patient where the practitionerhas pushed the device significantly into the patient and is obviouslyinserting into the bone.

FIG. 25 shows an even further protrusion of the device into the bone andthat is its stopping place as shown in FIG. 26 . FIG. 27 shows that theexemplary PecaBoo device has been screwed into the bone near the BCIbelow the knee joint itself. FIG. 28 is a close up of the image shown inFIG. 27 showing the same thing.

As noted above, after the device has been inserted into the bone nearthe BCI, the practitioner may, for example, remove the handle, removethe impact cap, and attach a syringe to the female luer which protrudesfrom the exposed portion of the hub after the impact cab has beenremoved. This is shown in FIG. 29 . Additionally seen in FIG. 29 is thered ring of the exemplary O-ring remaining on the hub as shown in theexpanded view of FIG. 17 , except here in FIG. 29 the O-ring is placedsecurely onto the hub which allows the tight fit of the yellow tri-lobehandle seen in FIGS. 23 and 26 . In the configuration of FIG. 29 , theset-up is ready for injection as per one of the above describedprotocols. FIG. 30 shows a close up of the view of FIG. 29 .

FIG. 31 now shows the syringe, which had been attached in the views ofFIGS. 29 and 30 , being removed. As noted above, when a practitionerinjects the medication into the patient in the set-up of FIGS. 29 and 30, he or she will often back out the exemplary PecaBoo delivery device sothat the medication can be injected into the cavity left behind. Thisbacking up and injecting may, for example, be repeated numerous times.Therefore, at the end of an injection, the exemplary delivery devicewill protrude less into the bone than it did at the beginning of theinjection. This is shown in FIG. 32 which shows the position of theprotrusion of the device as shown in FIG. 31 into the bone which is lessof a protrusion than that shown in FIGS. 27 and 29 , after the initialscrewing in of the delivery tool, as can readily be seen by comparison.

FIG. 33 shows a view from the other end of the patient, i.e., lookingupwards from the area of the patient's foot. This is a different patientthan shown in the previous figures. As seen in FIG. 33 , thepractitioner has just begun inserting an exemplary delivery device nearthe patient's knee joint in similar fashion as shown above. In thiscase, however, the exemplary delivery device is being inserted superiorto the patient's knee on the femoral side.

FIG. 34 shows a little bit of advance of the device and FIG. 35 shows ithaving been pushed in all the way such that the therapeutics can now bedelivered after removal of the tri-lobe handle and the impact cap. Thissituation is seen in FIG. 36 , where syringes are being attached to thefemale luer of the device.

FIG. 37 shows the protrusion of the exemplary device into the affectedarea on the femoral side of the joint. It is also noted in FIG. 37 thatthe patient has already had bone screw and other hardware inserted fromprior procedures.

FIG. 38 shows once again the device being inserted into the knee of apatient as described before, and FIG. 39 shows it having been protrudedquite some distance into the patient's body which was necessary giventhe patient's tissue width. FIG. 40 shows the device under fluoroscopyinto the bone superior to the knee joint corresponding with the view ofFIG. 39 . FIG. 41 shows the same patient now being made ready for theinjection, and FIG. 42 shows the injection using a syringe inserted intothe female lure of the exemplary device. FIG. 43 is another imageobtained from the fluoroscopic guidance as the practitioner wasperforming the injection.

FIG. 44 depicts another view of similar to that of FIG. 42 but from adifferent angle showing the device with the hub shown. FIG. 45illustrates an injection into that same patient as does FIG. 46 when theinjection has essentially been completed.

FIG. 47 shows the beginning of an exemplary procedure where the deviceis first inserted into a patient, and FIG. 48 shows the fluoroscopicguidance where the distal tip of the drill is just penetrating theposition inferior to the knee joint on the top of the tibia.

It will be understood that the images of FIGS. 23-48 are merelyexemplary and illustrate one example of the use of an exemplary deliverydevice according to the present invention with regard to patients withdegenerated cartilage, or for example, edema resulting from an ischemia,in the knee joint.

Thus, in exemplary embodiments of the present invention, for joints,such as, the knee, for example, there may be female luer locks tominimize air exposure. For PIARES, for example, the intradiscal system,the same system may be used. Alternatively, in each case—PIARES, PecaBooor the device of FIGS. 6-9 , in some exemplary embodiments there can beeither a fully closed system, using a septum, or, for example, one withfemale and male luer locks, minimizing air exposure.

Thus, in some embodiments a knee device, such as PecaBoo, may havefemale and male luer locks, and PIARES for intradiscal use may have aseptum and be a fully closed system. In others all of PIARES, PecaBooand other systems may be totally closed and use septums or the like.

Kits may be provided with each type, or with one type, either closedsystem or male and female luer locks, or a given kit may mix and match.Exemplary delivery devices may also be sold separately.

As noted above, in exemplary embodiments of the present invention, thedrill and hub, as shown in FIGS. 18A through 18C, for example, may bepreferably fabricated in one piece without seams, but may also beprovided in two pieces, as shown, with two pieces with a continuous 360degree welded seam fully sealing around where the drill passes throughthe hub. One piece is often preferred for reasons of cost as well. It isnoted that even when fabricated in one piece, in some exemplaryembodiments the hardened tip may still need to be made separately andwelded onto the distal end drill, as noted above.

Thus, in exemplary embodiments of the present invention, a surgical handtool can be provided, used for the non-invasive placement and deliveryof therapeutics, to a targeted site. This can be done through minimallyinvasive skin incision, or without any incision, as maybe desired. Thedelivery and placement of the therapeutic can be controlled and does notneed a powered drill or guide wire.

An exemplary device can have a closed pointed end, a threaded portion,and be provided with thread cutting/forming features, such as flute(s),and can have a shaft perforations to the central lumen at a distal endto deliver therapeutics or other preparations. At the proximal end,means can be provided to attach a syringe in communication with theshaft's central lumen, and there may be a keyed engagement feature forattachment of a hand grip. The delivery device can be made of sufficientlength to reach bone on either side of a desired or targeted joint, andto easily penetrate soft tissue and cortical bone to reach a targetedsite in cancellous bone adjacent to a cartilage defect.

The device's main shaft or drill portion can be made of hardenedstainless steel, or the like, such as, for example, 400 series or 17-40stainless steel, for example.

The device can have, for example, an attachable/removable hand grip forease of placement of the drill bit to a site, with a solid proximal endwith which to tap or hammer, and with a grip for torquing the devicethrough cortical bone and to guide a threaded shaft to a targeted sitein cancellous bone, for example. The grip can have an ergonomic form forease of use, such as a tri-lobe handle, which mimics the natural turn ofa wrist in 120 degree increments.

The device can have an impact cap to (i) provide impact anvil surface toprotect a proximal luer during impaction, as well as to (ii) close theluer opening to a shaft lumen.

The above-presented description and figures are intended by way ofexample only, and are not intended to limit the present invention in anyway except as set forth in the following claims. It is particularlynoted that persons skilled in the art can readily combine varioustechnical aspects of the elements of the various exemplary embodimentsdescribed above in numerous other ways, all of which are considered tobe within the scope of the invention.

1. A method for treating a patient for spinal disorders, said method comprising: identifying a repair-needing area of cartilage in a spinal joint that comprises a first vertebra and a second vertebra and a spinal disc therebetween; creating within said first vertebra a pathway to a bone-cartilage interface near said repair-needing area in said spinal joint; and delivering a first therapeutic material, through said pathway, sufficiently close to said bone-cartilage interface so that said method is effective to relieve pain, wherein said method comprises advancing a delivery device to a location within said first vertebra such that a distal end of said delivery device is located close to or at said bone-cartilage interface of said cartilage in said repair-needing area, and wherein said delivering said first therapeutic material comprises delivering said first therapeutic material through said delivery device.
 2. The method of claim 1, wherein said first therapeutic material comprises platelet-rich plasma.
 3. The method of claim 1, wherein said first therapeutic material comprises a granulocyte colony-stimulating factor.
 4. The method of claim 1, wherein said first therapeutic material comprises a granulocyte colony-stimulating factor, and wherein said delivering said first therapeutic material comprising said granulocyte colony-stimulating factor is followed by obtaining blood from said patient and producing platelet rich plasma from said blood and delivering said platelet rich plasma through said delivery device.
 5. The method of claim 1, further comprising delivering a clot-forming substance through said delivery device.
 6. The method of claim 5, wherein said clot-forming substance is selected from the group consisting of: a calcium chloride solution; and thrombin.
 7. The method of claim 1, wherein said location is such that said distal end of said delivery device is close to an interior edge of cortical bone and some other portion of said delivery device is located in or passes through cancellous bone.
 8. The method of claim 1, wherein said delivery device is externally threaded and said advancing comprises rotating said delivery device about a longitudinal axis of said delivery device.
 9. The method of claim 1, further comprising, after said advancing said delivery device but before said delivering of said first therapeutic material, partially retracting said delivery device so as to create an empty space for receiving said first therapeutic material, and delivering an amount of said first therapeutic material, and optionally repeating said retracting and said delivering.
 10. The method of claim 1, wherein said delivery device has at least one side port at or near a distal end thereof, such that said first therapeutic material can exit from said delivery device through said side port.
 11. The method of claim 1, wherein said introducing said delivery device is performed using imaging guidance, wherein said imaging guidance is selected from the group consisting of fluoroscopy and ultrasound guidance.
 12. The method of claim 1, further comprising performing said identifying step, said creating step, and said delivering said first therapeutic material step, on said second vertebra.
 13. The method of claim 1, further comprising delivering, at any time during said method, a second therapeutic material into said spinal disc between said first and second vertebrae.
 14. The method of claim 13, wherein said first therapeutic material and said second therapeutic material are identical to each other.
 15. The method of claim 13, wherein said delivering said second therapeutic material comprises delivering said second therapeutic material therapeutic simultaneously to a nucleus and an annulus of said spinal disc.
 16. The method of claim 13, wherein said delivering said second therapeutic material is performed using a device that comprises an outer needle and a longer inner needle suitable for introducing said second therapeutic material therethrough.
 17. The method of claim 13, wherein said delivering said second therapeutic material is performed using a device that comprises a puncturable septum that separates air inside said device from air outside said device.
 18. A method for treating a patient, said method comprising: identifying a repair-needing area of cartilage in a joint that comprises a first bone and a second bone; creating within said first bone a pathway to a bone-cartilage interface near said repair-needing area in said first bone; and delivering a first therapeutic material, through said pathway, sufficiently close to said bone-cartilage interface so that said method is effective to relieve pain, wherein said method comprises advancing a delivery device to a location within said first bone such that a distal end of said delivery device is located close to or at said bone-cartilage interface of said cartilage in said repair-needing area, and wherein said delivering said first therapeutic material comprises delivering said first therapeutic material through said delivery device, wherein said first therapeutic material comprises a Granulocyte Colony-Stimulating Factor.
 19. The method of claim 18, further comprising, after said delivering said first therapeutic material, obtaining blood from said patient, concentrating said obtained blood to form platelet rich plasma, and delivering said platelet rich plasma through said delivery device.
 20. The method of claim 18, wherein said first bone is a first vertebra and said second bone is a second vertebra, said first vertebra and said second vertebra being separated from each other by a spinal disc, and further comprising delivering, at any time during said method, a second therapeutic material into said spinal disc between said first and second vertebrae. 